Understanding The Early Course Of Schizophrenia: Findings From A Naturalistic, Prospective, Multi-Center Study

The aim of this dissertation was to provide a deeper understanding of the early phase of schizophrenia-spectrum disorders. We explored the one-year course of illness from multiple perspectives, including but not limited to the trajectories of psychotic symptoms, cognition, psychosocial and occupational functioning, as well as changes in brain network connectivity over time. The primary goal was to gain insights into the progression of the disorder, with a particular focus on how certain aspects of the illness may be predicted based on factors both prior to and in the early years after psychosis onset. To investigate this, data were used from an international, multi-center, naturalistic, prospective study (PSYSCAN) in individuals who had been recently diagnosed with a first psychotic episode in the context of a schizophrenia-spectrum disorder (FEP) as well as a healthy control cohort (HC). The observed variability in symptoms, cognition and psychosocial and occupational functioning confirms the importance of personalized psychiatry from a new angle. The research presented in this dissertation indicates that this heterogeneity not only exists in schizophrenia in general but even applies to patients in the early stage of illness (FEP), a patient group often approached as being homogenous in the current literature. It also highlights the value of advanced statistical methods in addressing the heterogeneity in FEP, e.g., providing the opportunity to investigate multiple predictors of outcome simultaneously (machine learning) or to identify patient subgroups with similar clinical profiles (clustering). This can help provide patients and their families/caregivers with a more accurate prognosis of the disease course following a first psychotic episode, and identify high-risk groups, such as those at increased risk of relapse, cognitive impairment, or functional difficulties. Ultimately, identifying these groups may, in turn, offer valuable insights for clinical practice by guiding treatment strategies, for example, determining which patients are most likely to benefit from cognitive training or require additional support in daily functioning. However, although these new techniques are well suited to address the heterogeneity in FEP in order to accurately predict prognosis and eventually contribute to more personalized treatment decisions, it is also evident that caution and nuance are critical when generalizing research findings from one patient cohort to another, and potentially even more so when translating them into real-world clinical practice.